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Immunology of B7-H1 and Its Roles in Human Diseases

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Abstract

B7-H1 was originally identified by homology analysis in comparison with B7-1 and B7-2, two molecules with important immunoregulatory functions. B7-H1, however, was broadly induced in the majority of peripheral tissues as well as hematopoietic cells. Upon binding to an as yet unidentified costimulatory receptor on primed T-cells, B7-H1 costimulates T-cell proliferation and preferentially induces interleukin 10 and interferon γ. The costimulatory function of B7-H1 may be critical for enhancing maturation and differentiation of T-cells in lymphoid organs. Conversely, by binding to programmed death 1 receptors on activated T-cells and B-cells, B7-H1 may inhibit ongoing T-cell responses in peripheral tissues by inducing apoptosis and arresting cell-cycle progression. Although a positive regulatory role of B7-H1 has been demonstrated in vitro and in various animal models, a negative regulatory role of B7-H1 has also been documented in human diseases, including cancer, rheumatoid arthritis, and human immunodeficiency virus infection. Delineation of the complex interactions between B7-H1 and its receptors as well as its interplay with other ligands is critical for understanding this new immunoregulatory system. Precise manipulation of B7-H1 and its receptors may provide unique opportunities for designing new disease treatments.

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References

  1. Chen L, Linsley PS, Hellstrom KE. Costimulation of T cells for tumor immunity.Immunol Today. 1993;14:483–486.

    Article  CAS  PubMed  Google Scholar 

  2. Chambers CA, Allison JP. Co-stimulation in T cell responses.Curr Opin Immunol. 1997;9:396–404.

    Article  CAS  PubMed  Google Scholar 

  3. Linsley PS, Ledbetter JA. The role of the CD28 receptor during T cell responses to antigen.Annu Rev Immunol. 1993;11:191–212.

    Article  CAS  PubMed  Google Scholar 

  4. Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation.Annu Rev Immunol. 1996;14:233–258.

    Article  CAS  PubMed  Google Scholar 

  5. Boise LH, Minn AJ, Noel PJ, et al. CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL.Immunity. 1995;3:87–98.

    Article  CAS  PubMed  Google Scholar 

  6. Allison JP, Krummel MF. The Yin and Yang of T cell costimulation.Science. 1995;270:932–933.

    Article  CAS  PubMed  Google Scholar 

  7. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion.Nat Med. 1999;5:1365–1369.

    Article  CAS  PubMed  Google Scholar 

  8. Tamura H, Dong H, Zhu G, et al. B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function.Blood. 2001;97:1809–1816.

    Article  CAS  PubMed  Google Scholar 

  9. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.J Exp Med. 2000;192:1027–1034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death.EMBO J. 1992;11:3887–3895.

    Article  CAS  Google Scholar 

  11. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.Immunity. 1999;11:141–151.

    Article  CAS  PubMed  Google Scholar 

  12. Petroff MG, Chen L, Phillips TA, Hunt JS. B7 family molecules: novel immunomodulators at the maternal-fetal interface.Placenta. 2002;23(suppl A):S95-S101.

    Article  PubMed  Google Scholar 

  13. Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation.Nat Immunol. 2001;2:261–268.

    Article  CAS  PubMed  Google Scholar 

  14. Tseng SY, Otsuji M, Gorski K, et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells.J Exp Med. 2001;193:839–846.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Swallow MM, Wallin JJ, Sha WC. B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFalpha.Immunity. 1999;11:423–432.

    Article  CAS  PubMed  Google Scholar 

  16. Yoshinaga SK, Zhang M, Pistillo J, et al. Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS.Int Immunol. 2000;12:1439–1447.

    Article  CAS  PubMed  Google Scholar 

  17. Wang S, Zhu G, Chapoval AI, et al. Costimulation of T cells by B7-H2, a B7-like molecule that binds ICOS.Blood. 2000;96:2808–2813.

    CAS  PubMed  Google Scholar 

  18. Hutloff A, Dittrich AM, Beier KC, et al. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28.Nature. 1999;397:263–266.

    Article  CAS  PubMed  Google Scholar 

  19. Mages HW, Hutloff A, Heuck C, et al. Molecular cloning and characterization of murine ICOS and identification of B7h as ICOS ligand.Eur J Immunol. 2000;30:1040–1047.

    Article  CAS  PubMed  Google Scholar 

  20. Coyle AJ, Lehar S, Lloyd C, et al. The CD28-related molecule ICOS is required for effective T cell-dependent immune responses.Immunity. 2000;13:95–105.

    Article  CAS  PubMed  Google Scholar 

  21. Tafuri A, Shahinian A, Bladt F, et al. ICOS is essential for effective T-helper-cell responses.Nature. 2001;409:105–109.

    Article  CAS  PubMed  Google Scholar 

  22. Grimbacher B, Hutloff A, Schlesier M, et al. Homozygous loss of ICOS is associated with adult-onset common variable immunode-ficiency.Nat Immunol. 2003;4:261–268.

    Article  CAS  PubMed  Google Scholar 

  23. Chapoval AI, Ni J, Lau JS, et al. B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production.Nat Immunol. 2001;2:269–274.

    Article  CAS  PubMed  Google Scholar 

  24. Sun M, Richards S, Prasad DV, Mai XM, Rudensky A, Dong C. Characterization of mouse and human B7-H3 genes.J Immunol. 2002;168:6294–6297.

    Article  CAS  PubMed  Google Scholar 

  25. Mazanet MM, Hughes CC. B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis.J Immunol. 2002;169:3581–3588.

    Article  CAS  PubMed  Google Scholar 

  26. Coyle AJ, Gutierrez-Ramos JC. The expanding B7 superfamily: increasing complexity in costimulatory signals regulating T cell function.Nat Immunol. 2001;2:203–209.

    Article  CAS  PubMed  Google Scholar 

  27. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.Nat Med. 2002;8:793–800.

    Article  CAS  PubMed  Google Scholar 

  28. Dong H, Chen L. B7-H1 pathway and its role in the evasion of tumor immunity.J Mol Med. 2003;81:281–287.

    Article  CAS  PubMed  Google Scholar 

  29. Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production.J Immunol. 2003;170:1257–1266.

    Article  CAS  PubMed  Google Scholar 

  30. Ishida M, Iwai Y, Tanaka Y, et al. Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues.Immunol Lett. 2002;84:57–62.

    Article  CAS  PubMed  Google Scholar 

  31. Yamazaki T, Akiba H, Iwai H, et al. Expression of programmed death 1 ligands by murine T cells and APC.J Immunol. 2002;169:5538–5545.

    Article  CAS  PubMed  Google Scholar 

  32. Curiel TJ, Wei S, Dong H, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity.Nat Med. 2003;9:562–567.

    Article  CAS  PubMed  Google Scholar 

  33. Trabattoni D, Saresella M, Biasin M, et al. B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression.Blood. 2003;101:2514–2520.

    Article  CAS  PubMed  Google Scholar 

  34. Nishimura H, Agata Y, Kawasaki A, et al. Developmentally regulated expression of the PD-1 protein on the surface of double-negative (CD4-CD8-) thymocytes.Int Immunol. 1996;8:773–780.

    Article  CAS  PubMed  Google Scholar 

  35. Agata Y, Kawasaki A, Nishimura H, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes.Int Immunol. 1996;8:765–772.

    Article  CAS  PubMed  Google Scholar 

  36. Nishimura H, Honjo T. PD-1: an inhibitory immunoreceptor involved in peripheral tolerance.Trends Immunol. 2001;22:265–268.

    Article  CAS  PubMed  Google Scholar 

  37. Nishimura H, Minato N, Nakano T, Honjo T. Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses.Int Immunol. 1998;10:1563–1572.

    Article  CAS  PubMed  Google Scholar 

  38. Shinkai Y, Rathbun G, Lam KP, et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement.Cell. 1992;68:855–867.

    Article  CAS  PubMed  Google Scholar 

  39. Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice.Science. 2001;291:319–322.

    Article  CAS  PubMed  Google Scholar 

  40. Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T. PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine.Proc Natl Acad Sci U S A. 2001;98:13866–13871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang S, Bajorath J, Flies DB, Dong H, Honjo T, Chen L. Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction.J Exp Med. 2003;197:1083–1091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Khong HT, Restifo NP. Natural selection of tumor variants in the generation of “tumor escape” phenotypes.Nat Immunol. 2002;3:999–1005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Smyth MJ, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance and immunotherapy.Nat Immunol. 2001;2:293–299.

    Article  CAS  PubMed  Google Scholar 

  44. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor.Annu Rev Immunol. 2001;19:683–765.

    Article  CAS  PubMed  Google Scholar 

  45. Akdis CA, Blaser K. Mechanisms of interleukin-10-mediated immune suppression.Immunology. 2001;103:131–136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chen L, McGowan P, Ashe S, et al. Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity.J Exp Med. 1994;179:523–532.

    Article  CAS  PubMed  Google Scholar 

  47. Chen L, McGowan P, Ashe S, Johnston JV, Hellstrom I, Hellstrom KE. B7-1/CD80-transduced tumor cells elicit better systemic immunity than wild-type tumor cells admixed withCorynebacterium parvum.Cancer Res. 1994;54:5420–5423.

    CAS  PubMed  Google Scholar 

  48. Stremmel C, Greenfield EA, Howard E, Freeman GJ, Kuchroo VK. B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4-dependent mechanism.J Exp Med. 1999;189:919–930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Maeda A, Yamamoto K, Yamashita K, et al. The expression of costimulatory molecules and their relationship to the prognosis of human acute myeloid leukaemia: poor prognosis of B7-2-positive leukaemia.Br J Haematol. 1998;102:1257–1262.

    Article  CAS  PubMed  Google Scholar 

  50. Pope B, Brown RD, Gibson J, Yuen E, Joshua D. B7-2-positive myeloma: incidence, clinical characteristics, prognostic significance, and implications for tumor immunotherapy.Blood. 2000;96:1274–1279.

    CAS  PubMed  Google Scholar 

  51. Salmon M, Gaston JS. The role of T-lymphocytes in rheumatoid arthritis.Br Med Bull. 1995;51:332–345.

    Article  CAS  PubMed  Google Scholar 

  52. Matsui T, Kurokawa M, Kobata T, et al. Autoantibodies to T cell costimulatory molecules in systemic autoimmune diseases.J Immunol. 1999;162:4328–4335.

    CAS  PubMed  Google Scholar 

  53. Dong H, Strome SE, Matteson EL, et al. Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis.J Clin Invest. 2003;111:363–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Third Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, 113-8603, Bunkyo-ku, Tokyo, Japan

    Hideto Tamura & Kiyoyuki Ogata

  2. Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA

    Haidong Dong & Lieping Chen

Authors
  1. Hideto Tamura
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  2. Kiyoyuki Ogata
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  3. Haidong Dong
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  4. Lieping Chen
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Correspondence to Hideto Tamura.

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Tamura, H., Ogata, K., Dong, H. et al. Immunology of B7-H1 and Its Roles in Human Diseases. Int J Hematol 78, 321–328 (2003). https://doi.org/10.1007/BF02983556

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  • DOI: https://doi.org/10.1007/BF02983556

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